CD8+ T cells recognize CagA-derived epitopes and mediate control of Helicobacter pylori infection
KOCH M. 1, SCHIEDE J. 1, ENGELSBERGER V. 1, FRIEDRICH V. 1, SCHEU S. 1, D'IPPOLITO E. 1, BUSCH D. 1, MEJÍAS-LUQUE R. 1, GERHARD M. 1
1 Institute for Medical Microbiology, Immunology and Hygiene, München, Germany
The potential of Helicobacter pylori to induce gastric cancer is primarily mediated by the activation of multiple pro-oncogenic pathways by the oncoprotein CagA, which is injected into host epithelial cells. This makes CagA a potential intracellular CD8+ T cell antigen. We recently showed that CagA proficient H. pylori strains induce a strong infiltration of CD8+ tissue-resident memory T (TRM) cells into the murine gastric mucosa. Here, we assessed CagA-specificity and functional properties of murine and human CD8+ T cells.
We infect C57BL/6 mice with various CagA-proficient and deficient H. pylori strains and study the gastric immune response natively and after T cell depletion. We analyze gastric biopsies and PBMCs from H. pylori infected patients with and without positive CagA serostatus.
In mice, almost all induced gastric CD8+ TRM cells are specific to CagA and respond with release of effector functions including Granzyme B secretion. The recognition of CagA and subsequent IFN-g secretion by CD8+ T cells mediates pathogen control in the early infection phase. We corroborate our findings of a CagA-dependent gastric CD8+ TRM cell infiltration in H. pylori infected patients. Importantly, we confirm CagA-specificity in humans and identify multiple CagA-derived CD8+ T cell epitopes.
The recognition of CD8+ T cell epitopes derived from a oncoprotein that is injected by an extracellular bacterium is a novel concept in CD8+ T cell immunity. It is of huge clinical significance since clearance of CagA-infected epithelium by cytotoxic CD8+ T cells could serve as a host protective mechanism to gastric cancer. Thus, CagA-specific CD8+ T cells could be of therapeutic use in future.